Sepsis is a systemic inflammatory response to infection, which causes organ failure and death in severe cases. It is an increasingly common cause of morbidity and mortality, particularly in elderly, immuno-compromised, and critically ill individuals. Sepsis has been reported to be the most common cause of death in the non-coronary intensive care unit (Bone R C et al; Chest. 1992 June; 101(6):1644-55). It occurs in 1-2% of all hospitalizations and mortality rates range from 20% for sepsis to 40% for severe sepsis to >60% for septic shock (a sub-category of severe sepsis) (Leibovici; Ann Intern Med 1991; 114(8):703, Martin et al; N Engl J. Med. 2003 Apr. 17; 348(16):1546-54).
The clinical definition of sepsis is the presence of two or more of the following conditions:
(1) fever (temperature >38° C.) or hypothermia (temperature <36° C.);
(2) heart rate >90 beats per minute;
(3) respiratory rate >20 breaths per minute or PaCO2<32 mm Hg; and
(4) white blood cell count >12 (x109 cells/L) or <4 (x109 cells/l), at the same time as a confirmed or suspected infection.
Conditions (1) to (4) are known as the SIRS (Severe Inflammatory Response Syndrome) criteria (Bone R C et al; Chest. 1992 June; 101(6):1644-55) and are a recognised international standard for diagnosis of severe inflammation. An individual exhibiting two or more of the SIRS criteria without a confirmed or suspected infection is classified as having non-infection associated SIRS.
The clinical definition of severe sepsis is sepsis as defined above, associated with sepsis-induced hypotension, organ dysfunction or perfusion abnormalities. Sepsis-induced hypotension is defined as a systolic blood pressure of <90 mm Hg or a reduction of <40 mm Hg from baseline in the absence of other causes of hypotension. Perfusion abnormalities may include, but are not limited to hypoperfusion, lactic acidosis, oliguria, or an acute alteration in mental status. Severe sepsis includes as a sub-category the condition of septic shock. This condition is specifically defined by the presence of sepsis-induced hypotension despite adequate fluid resuscitation along with the presence of perfusion abnormalities. Individuals who are receiving inotropic or vasopressor agents may not be hypotensive at the time that perfusion abnormalities are measured.
For the treatment of severe sepsis, diagnosis prior to the onset of the more severe symptoms (hypotension, organ dysfunction or hypoperfusion) with the institution of adequate treatment is of the utmost importance for a successful outcome (Rivers E et al. N Engl J Med 2001; 345(19): 1368-77). For example, Kumar et al showed that mortality was correlated to the number of hours passed after the onset of sepsis-induced hypotension before the first treatment was given (Kumar et al. Crit. Care Med 2006; 34(6):1589-96). A reliable biological or clinical marker to determine as early as possible whether an individual is at risk of developing severe sepsis is needed to minimise the delay before the institution of treatment,